Approaches Reveal a Key Role for DCs in CD4+ T Cell Activation and Parasite Clearance during the Acute Phase of Experimental Blood-Stage Malaria
Malaria is a significant health issue, particularly in the tropical and subtropical regions of the world. The red pulp (RP) of the spleen is a major site for the control of blood-borne infections such as malaria. Macrophages and dendritic cells (DCs) form a complex phagocyte network inside the splenic RP. DCs are usually thought of as highly efficient antigen-presenting cells that play an essential role in the activation of adaptive immunity. However, the direct role of DCs in the clearance of pathogens is still unclear. To clarify these issues, we took advantage of in vivo experimental approaches that enabled us to deplete or visualize DCs. The depletion of phagocytes demonstrated that DCs are key participants in the protection against blood stages of experimental malaria. Using confocal intravital microscopy, we observed that splenic RP DCs efficiently recognized and phagocytized infected erythrocytes during acute infection. We also showed that splenic DCs were crucial for the CD4+ T cell response to infection, but full DC maturation was achieved only after the peak of parasitemia. This study help to elucidate the protective mechanisms against Plasmodium parasites, and it shows that in vivo imaging is a reliable tool to evaluate iRBC phagocytosis during experimental malaria.
Vyšlo v časopise:
Approaches Reveal a Key Role for DCs in CD4+ T Cell Activation and Parasite Clearance during the Acute Phase of Experimental Blood-Stage Malaria. PLoS Pathog 11(2): e32767. doi:10.1371/journal.ppat.1004598
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.ppat.1004598
Souhrn
Malaria is a significant health issue, particularly in the tropical and subtropical regions of the world. The red pulp (RP) of the spleen is a major site for the control of blood-borne infections such as malaria. Macrophages and dendritic cells (DCs) form a complex phagocyte network inside the splenic RP. DCs are usually thought of as highly efficient antigen-presenting cells that play an essential role in the activation of adaptive immunity. However, the direct role of DCs in the clearance of pathogens is still unclear. To clarify these issues, we took advantage of in vivo experimental approaches that enabled us to deplete or visualize DCs. The depletion of phagocytes demonstrated that DCs are key participants in the protection against blood stages of experimental malaria. Using confocal intravital microscopy, we observed that splenic RP DCs efficiently recognized and phagocytized infected erythrocytes during acute infection. We also showed that splenic DCs were crucial for the CD4+ T cell response to infection, but full DC maturation was achieved only after the peak of parasitemia. This study help to elucidate the protective mechanisms against Plasmodium parasites, and it shows that in vivo imaging is a reliable tool to evaluate iRBC phagocytosis during experimental malaria.
Zdroje
1. Steiniger B, Barth P (2000) Microanatomy and function of the spleen. Adv Anat Embryol Cell Biol 151: III–IX, 1–101. 10592524
2. Mebius RE, Kraal G (2005) Structure and function of the spleen. Nat Rev Immunol 5: 606–616. doi: 10.1038/nri1669 16056254
3. Ishikawa-Sekigami T, Kaneko Y, Okazawa H, Tomizawa T, Okajo J, et al. (2006) SHPS-1 promotes the survival of circulating erythrocytes through inhibition of phagocytosis by splenic macrophages. Blood 107: 341–348. doi: 10.1182/blood-2005-05-1896 16141346
4. Hawkes M, Li X, Crockett M, Diassiti A, Finney C, et al. (2010) CD36 deficiency attenuates experimental mycobacterial infection. BMC Infect Dis 10: 299. doi: 10.1186/1471-2334-10-299 20950462
5. Hou TZ, Bystrom J, Sherlock JP, Qureshi O, Parnell SM, et al. (2010) A distinct subset of podoplanin (gp38) expressing F4/80+ macrophages mediate phagocytosis and are induced following zymosan peritonitis. FEBS Lett 584: 3955–3961. doi: 10.1016/j.febslet.2010.07.053 20682314
6. Leenen PJ, Radosevic K, Voerman JS, Salomon B, van Rooijen N, et al. (1998) Heterogeneity of mouse spleen dendritic cells: in vivo phagocytic activity, expression of macrophage markers, and subpopulation turnover. J Immunol 160: 2166–2173. 9498754
7. Jin C, Liang M, Ning J, Gu W, Jiang H, et al. (2012) Pathogenesis of emerging severe fever with thrombocytopenia syndrome virus in C57/BL6 mouse model. Proc Natl Acad Sci USA 109: 10053–10058. doi: 10.1073/pnas.1120246109 22665769
8. Sponaas AM, Freitas do Rosario AP, Voisine C, Mastelic B, Thompson J, et al. (2009) Migrating monocytes recruited to the spleen play an important role in control of blood stage malaria. Blood 114: 5522–5531. doi: 10.1182/blood-2009-04-217489 19837977
9. Coombes JL, Robey EA (2010) Dynamic imaging of host-pathogen interaction in vivo. Nat Rev Immunol 10: 353–364. doi: 10.1038/nri2746 20395980
10. Engwerda CR, Beattie L, Amante FH (2005) The importance of the spleen in malaria. Trends Parasitol 21: 75–80. doi: 10.1016/j.pt.2004.11.008 15664530
11. Pittet MJ, Weissleder R (2001) Intravital imaging. Cell 147: 983–991. doi: 10.1016/j.cell.2011.11.004
12. Junt T, Moseman EA, Iannacone M, Massberg S, Lang PA, et al. (2007) Subcapsular sinus macrophages in lymph nodes clear lymph-borne viruses and present them to antiviral B cells. Nature 450: 110–114. doi: 10.1038/nature06287 17934446
13. Sung JH, Zhang H, Moseman EA, Alvarez D, Iannacone M, et al. (2012) Chemokine guidance of central memory T cells is critical for antiviral recall responses in lymph nodes. Cell 150: 1249–1263. doi: 10.1016/j.cell.2012.08.015 22980984
14. Bockenstedt LK, Gonzalez DG, Haberman AM, Belperron AA (2012) Spirochete antigens persist near cartilage after murine Lyme borreliosis therapy. J Clin Invest 122: 2652–2660. doi: 10.1172/JCI58813 22728937
15. Ng LG, Hsu A, Mandell MA, Roediger B, Hoeller C, et al. (2008) Migratory dermal dendritic cells act as rapid sensors of protozoan parasites. PloS Pathog 4: e1000222. doi: 10.1371/journal.ppat.1000222 19043558
16. Amino R, Thiberge S, Martin B, Celli S, Shorte S, et al. (2006) Quantitative imaging of Plasmodium transmission from mosquito to mammal. Nat Med 12: 220–224. doi: 10.1038/nm1350 16429144
17. Tavares J, Formaglio P, Thiberge S, Mordelet E, Van Rooijen N, et al. (2013) Role of host cell traversal by the malaria sporozoite during liver infection. J Exp Med 210: 905–915. doi: 10.1084/jem.20121130 23610126
18. de Moraes LV, Tadokoro CE, Gomez-Conde I, Olivieri DN, Penha-Goncalves C (2013) Intravital placenta imaging reveals microcirculatory dynamics impact on sequestration and phagocytosis of Plasmodium-infected erythrocytes. PloS Pathog 9: e1003154. doi: 10.1371/journal.ppat.1003154 23382682
19. da Silva HB, Caetano SS, Monteiro I, Gomez-Conde I, Hanson K, et al. (2012) Early skin immunological disturbance after Plasmodium-infected mosquito bites. Cell Immunol 277: 22–32. doi: 10.1016/j.cellimm.2012.06.003 22784562
20. Martin-Jaular L, Ferrer M, Calvo M, Rosanas-Urgell A, Kalko S, et al. (2011) Strain-specific spleen remodelling in Plasmodium yoelii infections in Balb/c mice facilitates adherence and spleen macrophage-clearance escape. Cell Microbiol 13: 109–122. doi: 10.1111/j.1462-5822.2010.01523.x 20923452
21. Chotivanich K, Udomsangpetch R, McGready R, Proux S, Newton P, et al. (2002) Central role of the spleen in malaria parasite clearance. J Infect Dis 185: 1538–1541. doi: 10.1086/340213 11992295
22. Yap GS, Stevenson MM (1994) Differential requirements for an intact spleen in induction and expression of B cell-dependent immunity to Plasmodium chabaudi AS. Infect Immun 62: 4219–4225. 7927677
23. Buffet PA, Safeukui I, Deplaine G, Brousse V, Prendki V, et al. (2011) The pathogenesis of Plasmodium falciparum malaria in humans: insights from splenic physiology. Blood 117: 381–392. doi: 10.1182/blood-2010-04-202911 20852127
24. Yadava A, Kumar S, Dvorak JA, Milon G, Miller LH (1996) Trafficking of Plasmodium chabaudi adami-infected erythrocytes within the mouse spleen. Proc Natl Acad Sci USA 93: 4595–4599. doi: 10.1073/pnas.93.10.4595 8643449
25. Mebius RE, Nolte MA, Kraal G (2004) Development and function of the splenic marginal zone. Crit Rev Immunol 24: 449–464. doi: 10.1615/CritRevImmunol.v24.i6.40 15777163
26. Waite JC, Leiner I, Lauer P, Rae CS, Barbet G, et al. (2011) Dynamic imaging of the effector immune response to listeria infection in vivo. PloS Pathog 7: e1001326. doi: 10.1371/journal.ppat.1001326 21455492
27. Belyaev NN, Brown DE, Diaz AI, Rae A, Jarra W, et al. (2010) Induction of an IL7-R(+)c-Kit(hi) myelolymphoid progenitor critically dependent on IFN-gamma signaling during acute malaria. Nat Immunol 11: 477–485. doi: 10.1038/ni.1869 20431620
28. Banchereau J, Steinman RM (1998) Dendritic cells and the control of immunity. Nature 392: 245–252. doi: 10.1038/32588 9521319
29. Sponaas AM, Cadman ET, Voisine C, Harrison V, Boonstra A, et al. (2006) Malaria infection changes the ability of splenic dendritic cell populations to stimulate antigen-specific T cells. J Exp Med 203: 1427–1433. doi: 10.1084/jem.20052450 16754719
30. Voisine C, Mastelic B, Sponaas AM, Langhorne J (2010) Classical CD11c+ dendritic cells, not plasmacytoid dendritic cells, induce T cell responses to Plasmodium chabaudi malaria. Int J Parasitol 40: 711–719. doi: 10.1016/j.ijpara.2009.11.005 19968996
31. Guermonprez P, Helft J, Claser C, Deroubaix S, Karanje H, et al. (2013) Inflammatory Flt3l is essential to mobilize dendritic cells and for T cell responses during Plasmodium infection. Nat Med 19: 730–738. doi: 10.1038/nm.3197 23685841
32. Leisewitz AL, Rockett KA, Gumede B, Jones M, Urban B, et al. (2004) Response of the splenic dendritic cell population to malaria infection. Infect Immun 72: 4233–4239. doi: 10.1128/IAI.72.7.4233-4239.2004 15213168
33. Urban BC, Ing R, Stevenson MM (2005) Early interactions between blood-stage Plasmodium parasites and the immune system. Curr Top Microbiol Immunol 297: 25–70. 16265902
34. Ing R, Segura M, Thawani N, Tam M, Stevenson MM (2006) Interaction of mouse dendritic cells and malaria-infected erythrocytes: uptake, maturation, and antigen presentation. J Immunol 176: 441–450. doi: 10.4049/jimmunol.176.1.441 16365437
35. deWalick S, Amante FH, McSweeney KA, Randall LM, Stanley AC, et al. (2007) Cutting edge: conventional dendritic cells are the critical APC required for the induction of experimental cerebral malaria. J Immunol 178: 6033–6037. doi: 10.4049/jimmunol.178.10.6033 17475826
36. Krucken J, Mehnert LI, Dkhil MA, El-Khadragy M, Benten WP, et al. (2005) Massive destruction of malaria-parasitized red blood cells despite spleen closure. Infect Immun 73: 6390–6398. doi: 10.1128/IAI.73.10.6390-6398.2005 16177310
37. Seixas E, Moura Nunes JF, Matos I, Coutinho A (2009) The interaction between DC and Plasmodium berghei/chabaudi-infected erythrocytes in mice involves direct cell-to-cell contact, internalization and TLR. Eur J Immunol 39: 1850–1863. doi: 10.1002/eji.200838403 19585512
38. Bennett CL, Clausen BE (2007) DC ablation in mice: promises, pitfalls, and challenges. Trends Immunol 28: 525–531. doi: 10.1016/j.it.2007.08.011 17964853
39. Probst HC, Tschannen K, Odermatt B, Schwendener R, Zinkernagel RM, Van Den Broek M (2005) Histological analysis of CD11c-DTR/GFP mice after in vivo depletion of dendritic cells. Clin Exp Immunol 141: 398–404. doi: 10.1111/j.1365-2249.2005.02868.x 16045728
40. McGaha TL, Chen Y, Ravishankar B, van Rooijen N, Karlsson MC (2011) Marginal zone macrophages suppress innate and adaptive immunity to apoptotic cells in the spleen. Blood 117: 5403–5412. doi: 10.1182/blood-2010-11-320028 21444914
41. Stevenson MM, Tam MF, Belosevic M, van der Meide PH, Podoba JE (1990) Role of endogenous gamma interferon in host response to infection with blood-stage Plasmodium chabaudi AS. Infect Immun 58: 3225–32. 2119342
42. Muxel SM, Freitas do Rosario AP, Zago CA, Castillo-Méndez SI, Sardinha LR, et al. (2011) The spleen CD4+ T cell response to blood-stage Plasmodium chabaudi malaria develops in two phases characterized by different properties. PloS One 6: e22434. doi: 10.1371/journal.pone.0022434 21814579
43. Castillo-Mendez SI, Zago CA, Sardinha LR, Freitas do Rosario AP, Alvarez JM, et al. (2007) Characterization of the spleen B-cell compartment at the early and late blood-stage Plasmodium chabaudi malaria. Scand J Immunol 66: 309–319. doi: 10.1111/j.1365-3083.2007.01972.x 17635808
44. Grun JL, Long CA, Weidanz WP (1985) Effects of splenectomy on antibody-independent immunity to Plasmodium chabaudi adami malaria. Infect Immun. 48: 853–858. 3873415
45. Medeiros MM, da Silva HB, Reis AS, Barboza R, Thompson J, et al. (2013) Liver accumulation of Plasmodium chabaudi-infected red blood cells and modulation of regulatory T cell and dendritic cell responses. PLoS One 8: e81409. doi: 10.1371/journal.pone.0081409 24312297
46. McLachlan JB, Catron DM, Moon JJ, Jenkins MK (2009) Dendritic cell antigen presentation drives simultaneous cytokine production by effector and regulatory T cells in inflamed skin. Immunity 30: 277–288. doi: 10.1016/j.immuni.2008.11.013 19200757
47. Aoshi T, Zinselmeyer BH, Konjufca V, Lynch JN, Zhang X, et al. (2008) Bacterial entry to the splenic white pulp initiates antigen presentation to CD8+ T cells. Immunity 29: 476–486. doi: 10.1016/j.immuni.2008.06.013 18760639
48. Kursar M, Höpken UE, Koch M, Köhler A, Lipp M, et al. (2005) Differential requirements for the chemokine receptor CCR7 in T cell activation during Listeria monocytogenes infection. J Exp Med 201: 1447–1457. doi: 10.1084/jem.20041204 15851484
49. Ing R, Stevenson MM (2009) Dendritic cell and NK cell reciprocal cross talk promotes gamma interferon-dependent immunity to blood-stage Plasmodium chabaudi AS infection in mice. Infect Immun 77: 770–782. doi: 10.1128/IAI.00994-08 19015248
50. Dudziak D, Kamphorst AO, Heidkamp GF, Buchholz VR, Trumpfheller C, et al. (2007) Differential antigen processing by dendritic cell subsets in vivo. Science 315: 107–111. doi: 10.1126/science.1136080 17204652
51. Hochrein H, Shortman K, Vremec D, Scott B, Herzog P, et al. (2001) Differential production of IL-12, IFN-α and IFN-γ by mouse dendritic cell subsets. J Immunol 166: 5448–5455. doi: 10.4049/jimmunol.166.9.5448 11313382
52. Davies LC, Jenkins SJ, Allen JE, Taylor PR (2013) Tissue-resident macrophages. Nat Immunol 14: 986–995. doi: 10.1038/ni.2705 24048120
53. Ezekowitz RA, Gordon S (1982) Down-regulation of mannosyl receptor-mediated endocytosis and antigen F4/80 in bacillus Calmette-Guérin-activated mouse macrophages. Role of T lymphocytes and lymphokines. J Exp Med 155: 1623–1637.
54. Helmby H, Jönsson G, Troye-Blomberg M. (2000) Cellular changes and apoptosis in the spleens and peripheral blood of mice infected with blood-stage Plasmodium chabaudi chabaudi AS. Infect Immun 68: 1485–1490. doi: 10.1128/IAI.68.3.1485-1490.2000 10678964
55. Elias RM, Sardinha LR, Bastos KR, Zago CA, da Silva AP, et al. (2005) Role of CD28 in polyclonal and specific T and B cell responses required for protection against blood stage malaria. J Immunol 174: 790–799. doi: 10.4049/jimmunol.174.2.790 15634900
56. Freitas do Rosário AP, Muxel SM, Rodríguez-Málaga SM, Sardinha LR, Zago CA, et al. (2008) Gradual decline in malaria-specific memory T cell responses leads to failure to maintain long-term protective immunity to Plasmodium chabaudi AS despite persistence of B cell memory and circulating antibody. J Immunol 181: 8344–8355. doi: 10.4049/jimmunol.181.12.8344 19050251
57. da Silva HB, de Salles EM, Panatieri RH, Boscardin SB, Rodriguez-Málaga SM, et al. (2013) IFN-γ-induced priming maintains long-term strain-transcending immunity against blood-stage Plasmodium chabaudi malaria. J Immunol 191: 5160–5169. doi: 10.4049/jimmunol.1300462 24133169
58. Urban BC, Ferguson DJ, Pain A, Willcox N, Plebanski M, et al. (1999) Plasmodium falciparum-infected erythrocytes modulate the maturation of dendritic cells. Nature 400: 73–77. doi: 10.1038/21900 10403251
59. Wykes MN, Good MF (2008) What really happens to dendritic cells during malaria? Nat Rev Microbiol 6: 864–870. 18711429
60. Hadjantonakis AK, Macmaster S, Nagy A. (2002) Embryonic stem cells and mice expressing different GFP variants for multiple non-invasive reporter usage within a single animal. BMC Biotechnol 2: 11. doi: 10.1186/1472-6750-2-11 12079497
61. Lindquist RL, Shakhar G, Dudziak D, Wardemann H, Eisenreich T, et al. (2004) Visualizing dendritic cell networks in vivo. Nat Immunol 5: 1243–1250. doi: 10.1038/ni1139 15543150
62. Podoba JE, Stevenson MM. (1991) CD4+ and CD8+ T lymphocytes both contribute to acquired immunity to blood-stage Plasmodium chabaudi AS. Infect Immun 59: 51–58. 1898902
63. Spence PJ, Cunningham D, Jarra W, Lawton J, Langhorne J, et al. (2011) Transformation of the rodent malaria parasite Plasmodium chabaudi. Nat Protoc 6: 553–561. doi: 10.1038/nprot.2011.313 21455190
64. Reece SE, Thompson J. (2008) Transformation of the rodent malaria parasite Plasmodium chabaudi and generation of a stable fluorescent line PcGFPCON. Malar J 7: 183. doi: 10.1186/1475-2875-7-183 18808685
65. Jung S, Unutmaz D, Wong P, Sano G, De los Santos K, et al. (2002) In vivo depletion of CD11c+ dendritic cells abrogates priming of CD8+ T cells by exogenous cell-associated antigens. Immunity 17: 211–220. doi: 10.1016/S1074-7613(02)00365-5 12196292
66. Lepique AP, Daghastanli KR, Cuccovia IM, Villa LL (2009) HPV16 tumor associated macrophages suppress antitumor T cell responses. Clin Cancer Res 15: 4391–4400. doi: 10.1158/1078-0432.CCR-09-0489 19549768
Štítky
Hygiena a epidemiológia Infekčné lekárstvo LaboratóriumČlánok vyšiel v časopise
PLOS Pathogens
2015 Číslo 2
- Parazitičtí červi v terapii Crohnovy choroby a dalších zánětlivých autoimunitních onemocnění
- Očkování proti virové hemoragické horečce Ebola experimentální vakcínou rVSVDG-ZEBOV-GP
- Koronavirus hýbe světem: Víte jak se chránit a jak postupovat v případě podezření?
Najčítanejšie v tomto čísle
- Control of Murine Cytomegalovirus Infection by γδ T Cells
- ATPaseTb2, a Unique Membrane-bound FoF1-ATPase Component, Is Essential in Bloodstream and Dyskinetoplastic Trypanosomes
- Rational Development of an Attenuated Recombinant Cyprinid Herpesvirus 3 Vaccine Using Prokaryotic Mutagenesis and In Vivo Bioluminescent Imaging
- Direct Binding of Retromer to Human Papillomavirus Type 16 Minor Capsid Protein L2 Mediates Endosome Exit during Viral Infection